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Title 

Molecular basis of Bcl-XL-p53 interaction: Insights from molecular dynamics simulations

Authors 

N BharathamSeung-Wook ChiH S Yoon

Publisher 

Public Library of Science

Issue Date 

2011

Citation 

Plos One, vol. 6, no. 10, pp. e26014-e26014

Abstract 

Bcl-XL, an antiapoptotic Bcl-2 family protein, plays a central role in the regulation of the apoptotic pathway. Heterodimerization of the antiapoptotic Bcl-2 family proteins with the proapoptotic family members such as Bad, Bak, Bim and Bid is a crucial step in the apoptotic regulation. In addition to these conventional binding partners, recent evidences reveal that the Bcl-2 family proteins also interact with noncanonical binding partners such as p53. Our previous NMR studies showed that Bcl-XL: BH3 peptide and Bcl-XL: SN15 peptide (a peptide derived from residues S15-N29 of p53) complex structures share similar modes of bindings. To further elucidate the molecular basis of the interactions, here we have employed molecular dynamics simulations coupled with MM/PBSA approach. Bcl-XL and other Bcl-2 family proteins have 4 hydrophobic pockets (p1-p4), which are occupied by four systematically spaced hydrophobic residues (h1-h4) of the proapoptotic Bad and Bak BH3 peptides. We observed that three conserved hydrophobic residues (F19, W23 and L26) of p53 (SN15) peptide anchor into three hydrophobic pockets (p2-p4) of Bcl-XL in a similar manner as BH3 peptide. Our results provide insights into the novel molecular recognition by Bcl-XL with p53.

ISSN 

1932-6203

Link 

http://dx.doi.org/10.1371/journal.pone.0026014

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2017-04-19


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